Leonardo
da Vinci was probably the
first to describe the macroscopic appearance of atherosclerotic arteries. When
he illustrated the arterial lesions in an elderly man at autopsy, he suggested
that the thickening of the vessel wall might be due to “excessive nourishment”
from the blood. In general terms, Leonardo da Vinci’s conclusion still holds
true, yet another tribute to the great man’s tribute.

The term »arteriosclerosis«, a synonym of the term »atherosclerosis«, was
introduced by the German-born French surgeon and pathologist Johann G.C.F.M
Lobstein many years later in 1833. Lobstein considered arteriosclerosis as a
hardening of the arterial wall caused by the remodeling of the tissue in
response to ageing, metabolic dysfunction and hemodynamic stress.

The German physician Felix J. Marchand coined the term »atherosclerosis« (from
the Greek words »athere«, gruel and »scleros«, hard) to emphasize the
macroscopic features of the disease. In Anglophone regions, the word »atherosclerosis«
is often used synonymously with arteriosclerosis.
The word »atheromatosis« was coined by the London surgeon Joseph Hodgson in
1815 to describe the fatty degeneration characteristic of atherosclerotic
arteries. This term is still used as a synonym of arteriosclerosis or
atherosclerosis.Rudolf Virchow, a German pathologist and statesman, was the first to introduce
the idea of atherosclerosis as an inflammatory process; a concept that is
still valid today and is at the time of writing a field of very active
research.

Frequency and
clinical importance

Atherosclerosis
is a partly inflammatory, partly degenerative condition affecting the large
and medium-sized arteries. Most, perhaps even all, adults develop
atherosclerosis to some degree, so that the disease may be regarded as
ubiquitous. The important question, therefore, is not its absolute prevalence,
but the degree to which it causes clinically significant disease. This in turn
is related not so much to the atherosclerotic process per se but to the
complications it causes by either reducing the blood flow in the affected
artery, a process termed ischemia, or by provoking clotting of the blood in
the affected vessel. These clots may remain at the site of their formation and
are then called thrombi. Alternatively, they may break off in whole or in part
and be carried with the blood flow to cause blockage at some distant location.
Such moving blood clots are called emboli (plural of embolus). If a thrombus
is not large enough to block the artery completely, it may cause no symptoms
and gradually be incorporated into the atherosclerotic plaque. Indeed, many
older atherosclerotic lesions show histological evidence of incorporated
thrombi, so that this is probably the more likely fate of thrombi. However, a
large-enough thrombus may completely block (occlude) the artery in which it
forms, cutting off blood flow in the affected vessel. If this is an
end-vessel, i.e. the exclusive supply of an area of tissue, then this area of
tissue will be completely starved of oxygen and die in a process called
infarction.

About
40% of all deaths in developed countries are due to cardiovascular disease,
and most of these cardiovascular deaths are due to complications of
atherosclerosis (see Table 1 for data from Germany as an example of a Western
developed country). In Germany, for example, about 250.000 people suffer a
myocardial infarction every year. Despite improvements in intensive care,
about half of the people suffering a first myocardial infarction will die
within four weeks. A main reason for this is that in up to a half of all
cases, a first myocardial infarction occurs “out of the blue” without any
warning symptoms. These stark statistics underline the need for measures to
prevent myocardial infarction from occurring in the first place. These include
refraining from smoking, eating a balanced diet, taking regular exercise and
avoiding being overweight. Treatment of other risk factors, in particular high
cholesterol levels, high blood pressure or diabetes mellitus are also
important in reducing heart attack risk. As the world's population ages, and
as many countries improve economically, the impact of atherosclerosis
worldwide is set to increase dramatically in the next 30 years. A measure of
this is that in 2003, infectious disease was for the first time in the history
of mankind supplanted as the number one killer. This dubious distinction now
goes to atherosclerosis.

Major clinical
features and complications

As noted above,
many of the clinical features of atherosclerosis are due to the formation of a
thrombus at the site of an atherosclerotic plaque. When this occurs in the
heart, the result is a myocardial infarction, which is commonly known
in the US as a “coronary” and in Britain and its former colonies as a “heart
attack”. If the process occurs in the brain, the result is a stroke.
More rarely, blockage of an artery supplying the lower limb, or a kidney, or
part of the gut may occur, resulting in the death (necrosis) of these tissues.
A feature of atherosclerosis occurring particularly in the arteries of the
neck is that many small emboli may be formed over time causing temporary
blockage of small brain arteries. This may lead to multiple small strokes (transient
ischemic attacks) from which patients recover in a short space of time.
Such transient ischemic attacks require urgent attention, as they are often
the harbingers of a full-blown stroke. Finally, it has become clear in recent
years that many cases of dementia in the elderly are due not to Alzheimer's
disease, but to diffuse atherosclerosis of the arteries of the brain,
sometimes accompanied by multiple transient ischemic attacks. This is termed
vascular dementia.

Previously, it
was thought that clotting occurs mainly at the site of advanced disease.
However, more recent research has shown that smaller atherosclerotic plaques
termed “culprit lesions” are more often associated with thrombotic events.
These culprit lesions are metabolically active, and are characterized by a
soft lipid core covered by a fibrous cap. In most cases, the event leading to
thrombosis appears to be a tear of the fibrous cap in a process called plaque
rupture. This exposes the circulating blood to the interior of the
atherosclerotic lesion, which triggers the clotting cascade in the blood. In
some cases, it appears that thrombosis may occur even without rupture when
there is a break in the layer of cells lining the artery at the location of an
atherosclerotic plaque. Such a break in this layer of cells is termed
superficial erosion.

Other important
clinical features of atherosclerosis relate to the ability of some plaques to
reduce flow in the affected artery that the oxygen supply of the downstream
tissue is imperitted. An oxygen supply that is adequate under resting
circumstances may no longer be sufficient when tissue demand rises as, for
example, during exercise. This lack of oxygen causes pain in the affected
tissue. If this occurs in the heart, the result is angina pectoris, if
it occurs in the legs it results in a condition known as intermittent
claudication. A further important complication of atherosclerosis concerns
the aorta, which is the main artery leading from the heart. Atherosclerosis of
the aorta may weaken the wall of this vessel to such an extent that it bulges
out. This is called an aortic aneurysm. An aortic aneurysm may bleed
into the surrounding tissue, causing pain. Alternatively, and
catastrophically, it may burst, leading to massive internal bleeding and
sudden death.

Risk factors

Atherosclerosis is a complex
disease that does not occur for a single reason. Epidemiological studies have
identified factors that influence both the susceptibility to atherosclerosis
and its progression and outcome. Disease mediators that influence the clinical
outcome of atherosclerosis are termed “risk factors”. Risk factors may be
divided into those that can be modified and those that cannot. Non-modifiable
risk factors include age, male sex, certain genetic mutations and a positive
family history of early-onset atherosclerosis. The modifiable risk factors for
atherosclerosis include smoking, overweight and obesity, lack of exercise,
psychological stress, low social status, poor diet, high blood pressure, high
LDL, low HDL, high triglycerides, high levels of a lipoprotein called Lp(a),
and the presence of diabetes mellitus.